We have found that scavengers of products that are formed during the normal oxidative burst of polymorphonuclear leukocytes (PMN) can upregulate PMN phagocytosis. Methionine and taurine (which block n-chloramines and hypochlorous acid, respectively) increased the ingestion of IgG-coated sheep RBC (EIgG) by 3 to 5 fold. Like azide and catalase (which block earlier steps in the oxidative burst) these inhibitors also increased the adherence of EIgG to PMN, while having no effect on adherence of C3b-coated target cells. These results suggest that the long-lived, toxic products of myeloperoxidase (MPO)-H2O2-halide system are primarily responsible for downregulating PMN phagocytosis. These products appear to interfere with the function of PMN FcR, but not PMN CR1. We have shown that the phagocytic function of PMN of patients with acute bacterial infections is markedly upregulated, even in the absence of inhibitors of the oxidative burst. Longitudinal studies showed that the enhanced phagocytosis paralleled a reduction in superoxide anion production which was seen on the first day after hospital admission. Phagocytic activity and superoxide levels normalized as patients improved clinically. Enhanced phagocytosis in patient PMN was not associated with increased surface expression of the low-affinity PMN Fc receptors, FcRII or FcRIII; however, in 5 of 7 patients tested, there was a marked increase in the surface expression of high-affinity FcR (FcRI), which is not normally expressed on the surface of PMN. Unlike PMN, the extent of ingestion by patient monocytes (MO) was normal; however, kinetic studies showed that patient MO ingest EIgG significantly more rapidly than normal MO. Thus the IgG-dependent phagocytic capacity of both MO and PMN of patients with acute bacterial infections is upregulated. Soluble inflammatory mediators may play an important role in the enhanced phagocytosis in patient PMN. We have found that IL-1, IL- 2 and TNF each upregulate PMN phagocytosis in the absence of inhibitors of the oxidative burst. This effect was not related to increased expression of high or low-affinity FcR on the surface of PMN.